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背根神经节神经元的慢钠电导:神经元内的同质性和神经元间的异质性。

Slow sodium conductances of dorsal root ganglion neurons: intraneuronal homogeneity and interneuronal heterogeneity.

作者信息

Rizzo M A, Kocsis J D, Waxman S G

机构信息

Department of Neurology, Yale University School of Medicine, New Haven 06510.

出版信息

J Neurophysiol. 1994 Dec;72(6):2796-815. doi: 10.1152/jn.1994.72.6.2796.

Abstract
  1. Voltage-dependent Na+ conductances were studied in small (18-25 microns diam) adult rat dorsal root ganglion (DRG) neurons with the use of the whole cell patch-clamp technique. Na+ currents were also recorded from larger (44-50 microns diam) neurons and compared with those of the small neurons. 2. The predominant Na+ conductance in the small neurons was selective over tetramethylammonium by at least 10-fold and was resistant to 1 microM external tetrodotoxin (TTX). Na+ conductances in many larger DRG neurons were kinetically faster and, in contrast, were blocked by 1 microM TTX. 3. The Na+ conductance in the small neurons was kinetically slow. Activation half-times were voltage dependent and ranged from 2 ms at -20 mV to 0.7 ms at +50 mV. Approximately 50% of the activation half-time was comprised of an initial delay. Inactivation half-times were voltage dependent and ranged from 11 ms at -20 mV to 2 ms at +50 mV. 4. Peak slow Na+ conductances were near maximal with conditioning potentials negative to -120 mV and were significantly reduced or eliminated with conditioning potentials positive to -40 mV. The slow Na+ conductance increased gradually with test potentials extending from -40 to +40 mV. In some cells the conductance could be saturated at +10 mV. Peak conductance/voltage relationships, although stable in a given neuron, revealed marked variability among neurons, spanning > 20- and 50-mV domains for steady-state activation and inactivation (current availability), respectively. 5. Kinetics remained stable within a given neuron over the course of an experiment. However, considerable kinetic variation was exhibited from neuron to neuron, such that the half-times of activation and of inactivation spanned an order of magnitude. In all small neurons studied there appeared to be a singular kinetic component of the current, based on sensitivity to the conditioning potential, voltage dependence of activation, and inactivation half-time. 6. Unique closing properties were exhibited by Na+ channels of the small neurons. Hyperpolarization following a depolarization-induced fully inactivated state resulted in tail currents that appeared to be the consequence of reactivation of the slow Na+ conductance. Tail currents recorded at various times during a fixed level of depolarization revealed that the underlying channels accumulated into a volatile inactivated state over the course of the preceding depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)
摘要
  1. 运用全细胞膜片钳技术,对成年大鼠直径较小(18 - 25微米)的背根神经节(DRG)神经元中的电压依赖性钠离子电导进行了研究。还从直径较大(44 - 50微米)的神经元中记录了钠离子电流,并与小神经元的电流进行了比较。2. 小神经元中主要的钠离子电导对四甲基铵的选择性至少为10倍,并且对1微摩尔的细胞外河豚毒素(TTX)具有抗性。许多较大的DRG神经元中的钠离子电导在动力学上更快,相反,会被1微摩尔的TTX阻断。3. 小神经元中的钠离子电导在动力学上较慢。激活半衰期依赖于电压,范围从 - 20 mV时的2毫秒到 + 50 mV时的0.7毫秒。大约50%的激活半衰期由初始延迟组成。失活半衰期依赖于电压,范围从 - 20 mV时的11毫秒到 + 50 mV时的2毫秒。4. 当预处理电位为负至 - 120 mV时,峰值慢钠离子电导接近最大值,而当预处理电位为正至 - 40 mV时,峰值慢钠离子电导显著降低或消除。随着测试电位从 - 40 mV扩展到 + 40 mV,慢钠离子电导逐渐增加。在一些细胞中,电导在 + 10 mV时可能达到饱和。峰值电导/电压关系虽然在给定神经元中稳定,但在神经元之间显示出明显的变异性,稳态激活和失活(电流可用性)分别跨越 > 20 mV和50 mV的范围。5. 在实验过程中,给定神经元内的动力学保持稳定。然而,神经元之间表现出相当大的动力学差异,使得激活和失活的半衰期跨越一个数量级。基于对预处理电位的敏感性、激活的电压依赖性和失活半衰期,在所研究的所有小神经元中,电流似乎都有一个单一的动力学成分。6. 小神经元的钠离子通道表现出独特的关闭特性。去极化诱导的完全失活状态后的超极化导致尾电流,这似乎是慢钠离子电导重新激活的结果。在固定去极化水平期间不同时间记录的尾电流显示,在先前去极化过程中,潜在通道积累到一种易变的失活状态。(摘要截断于400字)

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